The proposed studies involve the in vivo investigation of a new class of antiviral thymidine analogs, developed in the same laboratory where IdUrd was conceived and synthesized. The therapeutic efficacy of one of these compounds, 5-iodo-5'-amino-2',5'-dideoxyuridine (AIU), in the treatment of experimental ocular herpes simplex (acute and chronic epithelial and stromal keratitis and uveitis), encephalitis, and cutaneous and genital herpes infections will be evaluated by clinical, virologic and histopathologic means. Determination of aqueous, cerebrospinal fluid and serum levels of AIU following systemic administration will be made, and in vitro studies of the peak drug levels equivalent to those noted will be performed. The effect of AIU on recurrence rates of ocular herpes keratitis and its effect on the persistence of latent virus in the trigeminal ganglion will be determined. Toxicologic, teratologic, and, when appropriate, in vivo therapeutic efficacy studies of other compounds in this family are proposed. In addition to AIU, the drugs under immediate consideration are 5-iodo-5'-amino-2',5'-dideoxycytidine (AIC), 5'-amino-5' deoxythymidine (ATdR), and 5-trifluoromethyl-5'-amino-2', 5'-dideoxyuridine (AF3U). AIU has been shown in prelminary studies to have in vitro an in vivo antiherpetic activity comparable to IdUrd but without demonstrable cytotoxic or teratologic side effects. AIU's lack of toxicity and specificity of action are related to the observation that a key step in its metabolism is mediated by a herpes simple specific enzyme system. Other drugs in this family have similar therapeutically important properties. Bulk synthesis of these compounds for animal studies is proposed. This proposal will make possible the expansion of these studies to include evaluation of the therapeutic and toxicologic properties of the compounds.